IL-6 is a cytokine also called B-cell stimulating factor 2 (BSF2) or interferon β2. IL-6 was discovered as a differentiation factor involved in the activation of B-cell lymphocytes (Non-Patent Document 1), and was later revealed, to be a multifunctional cytokine that influences the function of various cells (Non-Patent Document 2). It has been reported to induce maturation of T lymphocyte cells (Non-Patent Document 3).
IL-6 transmits its biological activity via two kinds of proteins on the cell. The first is the IL-6 receptor, which is a ligand-binding protein to which IL-6 binds, with a molecular weight of about 80 kDa (Non-Patent Documents 4 and 5). The IL-6 receptor is present in a membrane-bound form that penetrates the cell membrane. It is expressed on the cell membrane, and also as a soluble IL-6 receptor, which mainly consists of the extracellular region of the membrane-bound form.
Patent Document 1 describes various forms of anti-IL-6R (IL-6 receptor) antibodies, for example, humanized anti-IL-6R antibodies and chimeric anti-IL-6R antibodies. Patent Document 2 describes therapeutic agents for chronic rheumatoid arthritis and synovial cell growth inhibitors, which contain as an active ingredient an IL-6 antagonist such as an anti-IL-6R antibody. Patent Document 3 describes the treatment of diseases caused by IL-6 production, such as plasmacytosis, hyperimmunoglobulinemia, anemia, nephritis, cachexia, rheumatism, Castleman's disease, and mesangial proliferative nephritis. Patent Document 4 describes preventive and/or therapeutic agents, containing an anti-IL-6R antibody as an active ingredient, for sensitized T cell-mediated diseases, for example, multiple sclerosis, uveitis, chronic thyroiditis, delayed hypersensitivity, contact dermatitis, and atopic dermatitis.
Patent Document 5 describes therapeutic agents for systemic lupus erythematosus, which contain an anti-IL-6R antibody as an active ingredient. Patent Document 6 describes therapeutic agents for Crohn's disease, which contain an anti-IL-6R antibody as an active ingredient. Patent Document 7 describes therapeutic agents for pancreatitis, which contain an anti-IL-6R antibody as an active ingredient. Patent Document 8 describes therapeutic agents for psoriasis, which contain an anti-IL-6R antibody as an active ingredient. Furthermore, Patent Document 9 describes therapeutic agents for juvenile chronic arthritis, which contain, an anti-IL-6R antibody as an active ingredient. Patent Document 10 describes agents for suppressing neural invasion of a cell, which contain an anti-IL-6R antibody as an active ingredient, and teaches that they can inhibit human pancreatic cancer neuroinvasion.
Gemcitabine (hydrochloride) (Gemzar (Registered Trademark)) is a cytosine analog which inhibits DNA synthesis by inhibiting ribonucleotide reductase and competing with dCTP for incorporation into DNA, and is currently used as a therapeutic agent against some types of cancers such as pancreatic cancer. Gemcitabine is also used as a concomitant agent in radiotherapy; however, no significant improvement in the long-term survival of pancreatic cancer patients has been achieved. Furthermore, there have been some attempts using other effective combination therapies; however, no reports so far indicate the improvement of survival rate.
Prior art documents related to the present invention include:    Non-Patent Document 1: Hirano, T. et al., Nature (1986) 324, 73-76    Non-Patent Document 2: Akira, S. et al., Adv. in Immunology (1993) 54, 1-78    Non-Patent Document 3: Lotz, M. et al., J. Exp. Med. (1988) 167, 1253-1258    Non-Patent Document 4: Taga, T. et al., J. Exp. Med. (1987) 166, 967-981    Non-Patent Document 5: Yamasaki, K. et al., Science (1987) 241, 825-828    Patent Document 1: WO92/19759    Patent Document 2: WO96/11020    Patent Document 3: WO96/12503    Patent Document 4: WO98/42377    Patent Document 5: WO98/42377    Patent Document 6: WO99/47170    Patent Document 7: WO00/10607    Patent Document 8: WO02/3492    Patent Document 9: WO02/080969    Patent Document 10: WO2009/148148